TES

一种被第七染色体上的Tes基因编辑形成的蛋白质

Testin, TESS, 或Tes，一种被第七染色体上的Tes基因编辑形成的蛋白质。Tes是一个在焦点粘连处被发现的由421个氨基酸组成的47 kDa的蛋白质；对管理细胞活性有一定的影响。同时也对肿瘤的发展有一定的抑制作用。Tes基因位于第七染色体薄弱位置，2007年确认它有肿瘤抑制功能使之名声大旺。

物质简介

Testinalso known asTESSis aproteinthat in humans is encoded by theTESgenelocated onchromosome7.TES is a 47kDaprotein composed of 421amino acidsfound atfocal adhesionsand is thought to have a role in regulation ofcell motility.In addition to this, TES functions as atumoursuppressor.TheTESgene is located within a fragile region ofchromosome 7, and thepromoterelements of theTESgene have been shown to be susceptible tomethylation- this prevents theexpressionof the TES protein. TES came to greater prominence towards the end of 2007 as a potential mechanism for itstumour suppressor functionwas published.

TES

In December 2007, Boeda, Briggset al.showed that the third LIM domain of TES displaces Mena from its usual subcellular positions (focal adhesionsor the cell leading edge). The ENA/VASP protein family (of which Mena is a member) are anchored to specific proteins within the cell by apeptidemotif consisting of aphenylalanineresidue, followed by fourprolineresidues - known as a FPPPP motif. It is theEVH1 domainsof VASP/EVL proteins that directly contact the FPPPP motif. The precise architecture of TES:MENA binding was revealed byX-ray crystallography, and showed that the 3rd LIM domain of TES covered up the FPPPP binding site within Menas EVH1 domain.Isothermal titration calorimetryshowed that TES has a greater affinity for Mena than its canonical FPPPP ligand, as presented in the focal adhesion protein zyxin. Using microscopy it was shown that either over-expression ofGFP-tagged TES, or just the tagged third LIM domain displaced Mena from focal adhesions and reduced mean cell velocity.

These finding were significant given that Mena is often over-expressed incancercells, and is thought to be partly responsible for cancer cell motility, and therefore a factor in cancermetastasis. TES is conversely often not produced in cancer cells. It is possible that a drug designed to mimic TES's interaction with Mena could be used to prevent metastasis and thus development of secondary tumours in cancer patients. The work was widely reported in the British press (the work was carried out byCancer Research UK),and also in the international press.

Conformational

Based on the observations that:

Garvalovet al.propose that TES exists in two conformational states: A 'closed' state where the N & C halves of TES interact, obscuring the Zyxin binding site in LIM1, and an 'open' state where the Zyxin binding site is accessible and the two halves no-longer interact in the same fashion, if at all. The regulatory mechanism switching between the two states is not presently fully understood.

Phenotype[edit]

InRNAiexperiments, cells that had impaired TES expression showed an inability to correctly organise theirfocal adhesionsandactinstress fibres.

In gene knockout experiments,transgenicmice lacking both copies of the TES gene displayed an increased susceptibility totumourformation when challenged with a carcinogen. Mice retaining the TES gene were less susceptible: thus, TES is a tumour suppressor gene.

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